Work is in progress on molecular mechanisms of evolution of the genome of Escherichia coli. We have developed the hypothesis that two sequential duplications of a smaller, primitive genome resulted in a quadruplication of all primitive genes. These replicate genes are believed to have diverged in function, expanding the genetic capabilities of the bacterium. In our view, traces of these evolutionary events remain today in that genes whose function are related have a tendency to be disposed either 90 degrees or 180 degrees apart on the circular map of the E. coli genome. Statistical analysis has been applied. This project is being pursued experimentally by examining the extent of homology between different parts of the E. coli genome, using heteroduplex analysis of appropriate pairs of F' episomes or transducing phages. The project is also being extended by examining the topography of gene locations in other bacterial genera.